Silymarin diminishes oleic acid-induced lipid accumulation in HepG2 cells by modulating the expression of endoplasmic reticulum stress markers

• Published in: Journal of herbal medicine 2022-06, Vol.33, p.100565, Article 100565
• Main Authors: Malekpour-Dehkordi, Zahra, Nourbakhsh, Mitra, Shahidi, Minoo, Sarraf, Nazanin, Sharifi, Roya
• Format: Article
• Language: English
• Subjects: Endoplasmic reticulum (ER) stress; Non-alcoholic fatty liver disease (NAFLD); Silymarin
• ISSN: 2210-8033
• DOI: 10.1016/j.hermed.2022.100565

Non-alcoholic fatty liver disease (NAFLD) is a common metabolic disorder which presents with the accumulation of triglycerides in hepatocytes due to imbalances in the uptake, synthesis, export, and oxidation of fatty acids. Silymarin is a flavonolignan derived from milk thistle, a herbal medicine that has been used for centuries to treat liver disease. In this study, the effect of silymarin on genes involved in lipogenesis and endoplasmic reticulum (ER) stress was investigated in the cellular NAFLD model. HepG2 cells were treated with 0.5 mM oleic acid (OA) in the presence or absence of silymarin for 24 h, and subsequently, lipid accumulation was assessed by staining the cells with Oil red O as well as the measurement of intracellular triglyceride (TG) content with an enzymatic method. Real-time reverse transcription polymerase chain reaction (RT-PCR) was used to measure the expression of sterol regulatory element-binding protein-1 (SREBP-1), fatty acid synthase (FAS), Sirtuin 1 (SIRT1), TRB3, and ATF4. Lipid accumulation was increased in OA-treated hepatocytes, an effect that was attenuated by silymarin. The expression of FAS, SREBP-1, TRB3, and ATF4 was significantly increased in OA-treated HepG2 cells, while the expression of SIRT1 was decreased. Treatment with silymarin could successfully diminish SREBP-1, FAS, TRB3, and ATF4 gene expression while augmenting the expression of SIRT1. Silymarin not only efficiently reduces lipogenesis but also decreases ER stress, which is a critical parameter in lipogenesis. Therefore, silymarin might be considered an effective supplementary option in the treatment of liver steatosis.